Cardiorespiratory responses, nitric oxide production and inflammatory factors in patients with myocardial infarction after rehabilitation.

There is evidence that myocardial infarction (MI) patients have an inflammatory process that includes skeletal muscles, and exercise has been reported to reduce some inflammatory markers. The aim of this work was to study NO and some inflammatory markers in quadriceps muscle of MI patients before and after cardiac rehabilitation. Muscle biopsy was obtained in 17 MI patients before and after CR and only once in 11 healthy subjects. Several cardiorespiratory and metabolic parameters were evaluated and skeletal muscle levels of nitric oxide synthases, nitrate, nitrite, nitrotyrosine, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß), interleukin- 6 (IL-6) and CD154. After CR there was an increase in maximal oxygen consumption (21.2 ±â€¯1.4 vs 25.7 ±â€¯2.5 mL/kg/min, P < 0.0001); work load (116.2 ±â€¯14.9 vs 140 ±â€¯17 W, P < 0.0001); pulmonary ventilation (59.8 ±â€¯7,5 vs 73.8 ±â€¯11.6 L/min, P < 0.0001); anaerobic threshold (53.8% ±â€¯3.5% vs 60.2% ±â€¯3.3% of maximal VO2, P < 0.0001), maximal lactatemia (8.1 ±â€¯1.4 vs 9.3 ±â€¯1.5 mmol/L, P < 0.0001), and oxygen pulse (11.7 ±â€¯1.6 vs 14.0 ±â€¯1.9 mL/pulse, P < 0.0001). CSA of type I fibers increased (4380 ±â€¯1868 vs 5237 ±â€¯1530 µm2, P = 0.02), and nitrate (18.6 ±â€¯3.04 vs 20.7 ±â€¯2.0 ng/mg, P < 0.001). There was a negative correlation between BMI, fat%, waist and hip circumferences and NO synthase, nitrite and nitrate after CR. The inflammatory mediators were higher in patients than in control subjects and did not change with CR. TGF-ß correlated directly with nitrite and nitrate and inversely to other inflammatory factors. In conclusion, there is an increase of nitrate post CR, indicating a more effective NO production. TGF-ß was related to anti-inflammatory processes even before CR.

[Oxidative stress in soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats]. / Estrés oxidativo en los músculos soleo y extensor digitorum longus (EDL) de ratas espontáneamente hipertensas.

Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in micromol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-alpha) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 +/- 5.0 vs. 3.3 +/- 0.3, p<0.001; EDL 20.2 +/- 4.3 vs. 4.5 +/- 0.4, p<0.0037), iNOS (soleus 26.6 +/- 3.7 vs. 8.3 +/- 0.9; EDL 21.3 +/- 3.7 vs. 11.0 +/- 0.8, both p<0.0001) and TNF-alpha (soleus 2.2 +/- 0.5 vs. 0.6 +/- 0.1, p<0.05; EDL 1.9 +/- 0.2 vs. 0.6 +/- 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 +/- 1.4 vs. 30.3 +/- 1.2, p<0.00001); of nNOS (soleus 16.8 +/- 1.4 vs. 20.7 +/- 1.8, p< 0.05; EDL 13.6 +/- 1.3 vs. 21.9 +/- 1.8, p<.005) and nitrite in EDL (5.8 +/- 0.3 vs. 7.1 +/- 0.5, p<0.026).There was a positive correlation between TNF-alpha vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-alpha and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-alpha, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.

Estrés oxidativo en los músculos soleo y extensor digitorum longus (EDL) de ratas espontáneamente hipertensas / Oxidative stress in soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats

Las enfermedades sistémicas crónicas afectan el músculo esquelético, siendo la inflamación y el estrés oxidativo algunos de los mecanismos involucrados. El efecto de la hipertensión arterial esencial sobre el músculo esquelético no es bien conocido. Se estudiaron los músculos soleo y extensor digitorum longus (EDL) de ratas espontáneamente hipertensas (SHR), comparadas con las controles normotensas Wistar Kyoto (WKY). Se determinaron los niveles de nitritos y nitratos en µmoles/mg-proteína; las sintasas del óxido nítrico: endotelial (eNOS); neuronal (nNOS); e inducible (iNOS), nitrotirosina y el factor de necrosis tumoral-alfa (TNF-α) en ng/mg-proteína. En las SHR, en el soleo y el EDL respectivamente, se incrementó la nitrotirosina (24,4 ± 5,0 vs. 3,3 ± 0,3, p<0,001; 20,2 ± 4,3 vs. 4,5 ± 0,4, p<0,0037), iNOS (26,6 ± 3,7 vs. 8,3 ± 0,9; 21,3 ± 3,7 vs. 11,0 ± 0,8 ambos p<0,0001), y TNF-α (2,2 ± 0,5 vs. 0,6 ± 0,1, p<0,05; 1,9 ± 0,2 vs. 0,6 ± 0,1, p<0,02); hubo disminución de eNOS en el soleo (20,6 ± 1,4 vs. 30,3 ± 1,2, p<0,00001); de nNOS (soleo 16,8 ± 1,4 vs. 20,7 ± 1,8, p< 0,05; EDL 13,6 ± 1,3 vs. 21,9 ± 1,8, p<0,005) y de nitrito en el EDL (5,8 ± 0,3 vs. 7,1 ± 0,5, p<0,026). En las SHR se observó correlación positiva entre TNF-α vs. nitrotirosina: soleo (r=0,798; p<0,031) y tendencia en EDL (r=0,739; p<0,057); iNOS vs. nitrotirosina (soleo: r=0,908 p<0,0001; EDL: r=0,707; p=0,01), tendencia entre TNF-α vs. iNOS en EDL (r=0,736; p=0,059); y correlación negativa entre eNOS vs. nitrotirosina en soleo (r=-0,816; p=0,0012). En conclusión, las SHR presentan un proceso inflamatorio muscular, evidenciado por el incremento de TNF-α, nitrotirosina, e iNOS. La disminución de las sintasas constitutivas, con incremento de la iNOS es evidencia de la disfunción endotelial.

Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in µmol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-α) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 ± 5.0 vs. 3.3±0.3, p<0.001; EDL 20.2 ± 4.3 vs. 4.5 ± 0.4, p<0.0037), iNOS (soleus 26.6 ± 3.7 vs. 8.3 ± 0.9; EDL 21.3 ± 3.7 vs. 11.0 ± 0.8, both p<0.0001) and TNF-α (soleus 2.2 ± 0.5 vs. 0.6 ± 0.1, p<0.05; EDL 1.9 ± 0.2 vs. 0.6 ± 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 ± 1.4 vs. 30.3 ± 1.2, p<0.00001); of nNOS (soleus 16.8 ± 1.4 vs. 20.7 ± 1.8, p< 0.05; EDL 13.6 ± 1.3 vs. 21.9 ± 1.8, p<0.005) and nitrite in EDL (5.8 ± 0.3 vs. 7.1 ± 0.5, p<0.026).There was a positive correlation between TNF-α vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-α and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-α, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.

Gender and skeletal muscle characteristics in subjects with chronic obstructive pulmonary disease.

BACKGROUND: The influence of gender in the clinical expression of COPD has received important attention. Limited information exists regarding gender differences in the skeletal muscle characteristics in COPD subjects. The present study was aimed to determine the differences in the skeletal muscle characteristics in men and women with and without COPD. METHODS: For comparison we studied 24 female (61 ± 9 years) and 30 male (65 ± 8 years) COPD patients with similar disease severity. In addition healthy subjects, 17 women (58 ± 8 years), and 9 men (57 ± 8 years) were studied. Pulmonary function, health status, six minute walk distance test (6MWD) and vastus lateralis muscle biopsy were assessed. Fiber type proportion, fiber type cross sectional area (CSA), capillary counts, and activity of citrate synthase (CS), 3-hydroxyacyl-CoA-dehydrogenase (HAD) and lactate-dehydrogenase (LDH) were determined. RESULTS: Pulmonary function, health status and 6MWD were similar in male and female COPD patients. Fiber type distribution was similar between women (I = 42 ± 9%, IIA = 39 ± 13%, IIX = 19 ± 7%) and men (I = 39 ± 13%, IIA = 38 ± 9%, IIX = 29 ± 10%) with COPD, as well as CSA, capillarity and enzymes (CS 8.59 ± 1.6 vs.9.74 ± 2.6, HAD 9.03 ± 1.9 vs. 9.84 ± 2.5, LDH 124 ± 48 vs. 151 ± 68 µmol min(-1) g(-1)). In normal subjects a decrease in type IIX fibers CSA was found in women compared with men (3703 ± 1478 vs. 5426 ± 1386 µm(2), respectively). CONCLUSIONS: Female and male with COPD have similar skeletal muscle characteristics; it is possible that the disease blurs the gender differences. On the other hand, there seems to be fewer differences in muscle characteristics between older men and women, perhaps due to lower male testosterone levels and physical inactivity.

[Lactate dehydrogenase isozymes in skeletal muscle of patients with chronic obstructive pulmonary disease]. / Isoenzimas de lactatodeshidrogenasa en el músculo esquelético de pacientes con EPOC.

INTRODUCTION AND OBJECTIVES: In patients with chronic obstructive pulmonary disease (COPD), lactate dehydrogenase (LDH) levels in skeletal muscles are normal or tend to be elevated; on exercise, these levels increase more rapidly than in individuals without COPD. As it is likely that concentrations of LDH isozymes LDH(4) and LDH(5) are elevated in such patients, we measured those isozymes in peripheral muscle of patients with COPD. PATIENTS AND METHODS: Eighteen patients with COPD and 10 healthy nonsmokers were included in the study. Spirometry and the 6-minute walk test were performed, and a biopsy of the quadriceps muscle was taken to measure levels of both total LDH and LDH isozymes by agarose gel electrophoresis and to classify the types of muscle fibers. RESULTS: Controls and patients had similar concentrations of total LDH (mean [SE], 130 [30]micromol/min/g vs 152 [50]micromol/min/g, respectively) and LDH isozymes. A subgroup of 5 patients showed increased levels of isozymes LDH(1), LDH(2), and LDH(3), with decreased LDH(5) levels; these patients were women and had a lower oxygen saturation. The LDH(5) level was directly correlated with the 6-minute walk test and oxygen saturation. The percentage of type IIA fibers correlated directly with LDH(3) and LDH(4) concentrations whereas type IIX fibers were inversely correlated with LDH(3) concentration. CONCLUSION: Measurement of LDH isozyme concentrations enabled a subgroup of patients to be identified with a higher concentration of cardiac isoenzymes and lower concentration of muscle isoenzymes, a situation which might indicate adaptation that favors aerobic metabolism.

Isoenzimas de lactatodeshidrogenasa en el músculo esquelético de pacientes con EPOC / Lactate Dehydrogenase Isozymes in Skeletal Muscle of Patients With Chronic Obstructive Pulmonary Disease

Introducción y objetivos. En los pacientes con enfermedad pulmonar obstructiva crónica (EPOC), las cifras de la enzima lactatodeshidrogenasa (LDH) en los músculos esqueléticos son normales o tienen cierta tendencia a aumentar; cuando dichos pacientes hacen ejercicio, los valores se elevan más rápidamente que en personas sin la enfermedad. Es probable que las concentraciones de las isoenzimas 4 y 5 de la LDH puedan estar aumentadas en estos pacientes, por lo que se han determinado las isoenzimas de la LDH en el músculo periférico de pacientes con EPOC. Pacientes y métodose ha estudiado a 18 pacientes con EPOC y a 10 personas sanas no fumadoras. Se les realizaron pruebas de función pulmonar, la prueba de la marcha de 6min y biopsia del músculo cuádriceps para medir tanto la LDH total como las isoenzimas de la LDH por electroforesis en gel de agarosa, así como para clasificar los tipos de fibras. Resultadoslas concentraciones de LDH total (media¡Àerror estándar: 130¡À30 frente a 152¡À50¦Ìmol/min/g) y sus isoenzimas fueron similares en controles y pacientes. Un subgrupo de 5 pacientes mostró un aumento de las isoenzimas LDH1, LDH2 y LDH3, con disminución de la LDH5; estos pacientes eran mujeres y tenían menor saturación de oxígeno. El valor de la LDH5 se relacionó directamente con la prueba de la marcha de 6min y la saturación de oxígeno. El porcentaje de fibras IIA mostró una correlación directa con la concentración de LDH3 y LDH4, y las fibras IIX se relacionaron inversamente con la LDH3. Conclusión. A partir de las concentraciones de las isoenzimas de la LDH se pudo identificar a un subgrupo de pacientes con una concentración mayor de las isoenzimas cardíacas y menor de las musculares, lo que eventualmente podría representar una adaptación que favorezca el metabolismo aeróbico(AU)

Introduction and Objectives. In patients with chronic obstructive pulmonary disease (COPD), lactate dehydrogenase (LDH) levels in skeletal muscles are normal or tend to be elevated; on exercise, these levels increase more rapidly than in individuals without COPD. As it is likely that concentrations of LDH isozymes LDH4 and LDH5 are elevated in such patients, we measured those isozymes in peripheral muscle of patients with COPD. Patients and MethodsEighteen patients with COPD and 10 healthy nonsmokers were included in the study. Spirometry and the 6-minute walk test were performed, and a biopsy of the quadriceps muscle was taken to measure levels of both total LDH and LDH isozymes by agarose gel electrophoresis and to classify the types of muscle fibers. ResultsControls and patients had similar concentrations of total LDH (mean [SE], 130 [30]¦Ìmol/min/g vs 152 [50]¦Ìmol/min/g, respectively) and LDH isozymes. A subgroup of 5 patients showed increased levels of isozymes LDH1, LDH2, and LDH3, with decreased LDH5 levels; these patients were women and had a lower oxygen saturation. The LDH5 level was directly correlated with the 6-minute walk test and oxygen saturation. The percentage of type IIA fibers correlated directly with LDH3 and LDH4 concentrations whereas type IIX fibers were inversely correlated with LDH3 concentration. ConclusionMeasurement of LDH isozyme concentrations enabled a subgroup of patients to be identified with a higher concentration of cardiac isoenzymes and lower concentration of muscle isoenzymes, a situation which might indicate adaptation that favors aerobic metabolism(AU)

Morphological alterations in skeletal muscle of spontaneously hypertensive rats.

The Extensor digitorum longus (EDL) and the soleus muscles of spontaneously hypertensive rats (SHR) were studied in comparison with those of their normal counterparts, the Wistar Kyoto (WKY) rats. Quantitative assessment of capillaries and muscle fibre typing was done with optical microscopy, while the study of capillary abnormalities was performed by ultrastructural observation. There were no differences in fibre type proportion or in capillarity indexes between the SHR and the control rats. A reduction in the area of IIB fibres was found in the EDL muscle of the hypertensive animals. The ultrastructural study showed abnormalities in the capillaries of both muscles in SHR, the cross section of the endothelial cells was enlarged; there was irregular distribution of caveolae and pinocytic vesicles, the capillary basement membrane showed irregular width, with parts engrossed and reduplicated. Some pericytes were prominent. There were macrophages present in the interstitial space. In some muscle fibres there was disorganization of the sarcomere structure, swelling of the sarcotubular system, abundant autophagic vacuoles, and proliferative satellite cells. There were abundant collagen fibrils. The presence of cellular rests, autophagic vacuoles and loss of sarcolemma indicated necrosis. It can be concluded, that in SHR, muscle capillaries showed alterations that may be the substrate of functional rarefaction, although anatomical rarefaction (number reduction) could not be demonstrated. In EDL and soleus muscles of SHR, signs of a mild myopathy with focal fibrosis were present.

Peripheral muscle alterations in non-COPD smokers.

BACKGROUND: Although tobacco smoke is the main cause of COPD, relatively little attention has been paid to its potential damage to skeletal muscle. This article addresses the effect of smoking on skeletal muscle. METHODS: The vastus lateralis muscle was studied in 14 non-COPD smokers (FEV(1)/FVC, 78 +/- 5%) and 20 healthy control subjects (FEV(1)/FVC, 80 +/- 3%). Muscular structure, enzyme activity, constitutive and inducible nitric oxide (NO) synthases (endothelial NO oxide synthase [eNOS], neuronal NO synthase [nNOS] and inducible NO synthase [iNOS]), nitrites, nitrates, nitrotyrosine, and the presence of macrophages were analyzed. RESULTS: In smokers, type I muscle fibers cross-sectional area was decreased, and a similar trend was found in type IIa fibers. Lactate dehydrogenase levels and the percentage of fibers with low oxidative and high glycolytic capacity were increased in smokers. nNOS (96.9 +/- 11.7 vs 125.4 +/- 31.9 ng/mg protein; p < 0.01) and eNOS (38.9 +/- 11.0 vs 45.2 +/- 7.7 ng/mg protein [+/- SD]; p < 0.05) were lower in smokers, while fiber type distribution, capillarity measures, beta-hydroxy-acyl-CoA-dehydrogenase levels, iNOS, nitrite, nitrate, and nitrotyrosine levels, and macrophage number in the muscle tissue were similar to the nonsmoker subjects. CONCLUSIONS: Smokers presented some alterations of skeletal muscle such as oxidative fiber atrophy, increased glycolytic capacity, and reduced expression of the constitutive NO synthases (eNOS and nNOS). The findings support some muscular structural and metabolic damage but not the presence of local inflammation in the smokers. In addition, they suggest a possible effect of tobacco smoke impairing the normal process of NO generation.

Carazterísticas musculares y potencia anaeróbica y aeróbica máximas en ciclistas de competición / Muscle characteristics and anaerobic and aerobic maximal power in competence cyclists

Se estudiaron 15 ciclistas de la selección del Estado Lara de Venezuela, 9 del sexo masculino y 5 del femenino, de 20± 2 años. Siete eran fondistas, 4 semifondistas y 4 velocistas. La potencia aeróbica fue evaluada por el consumo máximo de oxígeno (VO2 max), la potencia anaeróbica lactácida por la prueba de Wingate y la potencia anaeróbica alactácida por la prueba del salto vertical. Se practicó biopsia del músculo cuadriceps para la clasificación de los tipos de fibras, evaluación de los capilares y determinación de las enzimas citrato sintetasa (CS), ß-hidroxiacil-CoA-deshidrogenasa(HAD) y deshidrogenasa láctica (LDH). El grupo masculino alcanzó mayores valores en todas las pruebas, excepto en el índice de fatiga en el que no difirió del grupo femenino. El músculo mostró niveles más altos de CS en los hombres y fue similar en área de las fibras y en capilaridad respecto a las mujeres. Los fondistas mostraron mayor proporción de fibras tipo I (63±7 %), mayor nivel de CS (29,2±5,5 μmol/min.gr) y mayor densidad capilar (417±31capilares /mm2). Los mediofondistas presentaron mayor porcentaje de fibras tipo IIa (50±5 %). Se encontró correlación entre la CS y los Watts/kg en la prueba del salto (r=0,55), entre la HAD y la potencia promedio/kg en Wingate (r=0,69)y entre la LDH y los resultados de Wingate (r=0,52 a r=0,60).En conclusión, las potencias aeróbica y anaeróbica de los ciclistas del grupo estudiado parecen estar más relacionadas con los efectos del entrenamiento en el músculo, que con su composición miofibrilar (AU)

A group of Venezuelan cyclists from the Lara State selection, aged 20 ± 2 years, formed by 9 males and 5 females, wasstudied. Seven of them were long-distance cyclists, 4 sprinters and 4 middle-distance cyclists. Maximal aerobic power(VO2 max) was evaluated, as well as lactacid (Wingate test) and alactacid power (vertical jump test). A quadriceps musclebiopsy was taken for muscle fiber classification, assessment of capillaries and determination of the enzymes citrate synthase (CS), ß-hydroxacil-CoA-dehydrogenase (HAD) and lactic dehydrogenase (LDH). The male group showed higher values in all tests, except in fatigue index, which was similar to the female group. CS muscle levels were higherin men, but there were not differences in fiber area and capillarity compared to females. The highest percentage in typeI fibers was found in the long-distance cyclists (63±7 %), also the most elevated CS level (29.2±5.5 μmol/min.gr) and the highest capillary density (417±31 capillaries/mm2). Middle-distance cyclists showed the highest proportion of IIafiber type (50±5 %). There was a direct correlation between CS level and Watts/Kg in the jumping test (r=.55), in the HAD level and mean power/Kg in Wingate test (r=0.69), and between LDH level and the all the results of the Wingatetest (r=0.52 to r=0.60).In conclusion, in this group of cyclist, aerobic and anaerobic power tests seemed to be more related to muscle changes due to training that to muscle fiber type proportions (AU)

Alteraciones musculares periféricas en la enfermedad de Chagas

La enfermedad de Chagas sigue siendo un problema en Venezuela y en varios países de Latinoamérica. Este trabajo presenta datos sobre las alteraciones que esta enfermedad produce en los músculos esqueléticos periféricos, lo cual puede contribuir a la incapacidad funcional que presentan muchos de los pacientes. Fueron estudiados 19 pacientes con enfermedad avanzada, a quienes se les hizo evaluación cardiorrespiratoria, ecocardiograma, prueba de ejercicio y biopsia del músculo cuádriceps. El 42% presentó incapacidad funcional moderada a severa, medida por el consumo máximo de oxígeno, que estuvo relacionada con cambios morfológicos y metabólicos en las fibras musculares. Se hallaron alteraciones en la microvasculatura muscular compatibles con daño autoinmune. En conclusión, los pacientes con enfermedad de Chagas sufren alteraciones en la musculatura periférica que puede contribuir a la incapacidad funcional y al grado de afectación por esta enfermedad. La determinación de la capacidad funcional debería agregarse a la evaluación de la enfermedad

Chagas disease is still a problem in Venezuela and other Latin American countries, in spite of efforts to control the disease. Peripheral muscle alterations that contribute to decreased functional capacity in moderate to advanced Chagas’ disease patients are analyzed in the present work. Nineteen Chagas’ disease patients were studied, including cardio-respiratory evaluation, echocardiogram, exercise test and quadriceps muscle biopsy. The results showed 42% patients with moderate to severe decrease of maximal oxygen consumption. Muscle biopsies presented morphologic and metabolic alterations, some related to functional capacity. Capillary vessel damage in muscle was similar to that found in autoimmune diseases. In conclusion, Chagas’ disease patients showed peripheral muscle alterations related to decreased functional capacity. The functional capacity changes may contribute to the severity of the disease and should be added to the evaluation of the patients

Peripheral muscle composition and health status in patients with COPD.

STUDY OBJECTIVE: The present study evaluated the relationship between health status (HS) and peripheral muscle histochemical characteristics in chronic obstructive pulmonary disease (COPD), and identified selected independent respiratory and extrapulmonary variables that predicted the HS of these patients. DESIGN: Cross-sectional study. SETTING: Outpatient respiratory clinic of a university hospital. PATIENTS AND METHODS: We studied 29 patients (63+/-10 yrs) with a forced expiratory volume in 1s (FEV1) of 39+/-12%. All patients underwent vastus lateralis muscle biopsies for histochemical analysis. They also had spirometry, arterial blood gas analysis, body mass index (BMI), dyspnea determined with the MMRC scale and responded to the St. George's Respiratory Questionnaire (SGRQ) for HS assessment. RESULTS: SGRQ total score correlated with fiber type distribution. A stepwise multiple regression identified three independent predictors of SGRQ total score: type I fiber proportion, BMI, and FEV1; r = 0.78 and r2 = 0.61. CONCLUSIONS: These results indicate that impaired HS in COPD is related to the peripheral muscle changes characterized by less type I fibers proportion. The findings argue in favor of an important contribution of the systemic consequences on the HS in COPD independently from the airflow limitation severity, and help to explain the observation of the poor correlation between the degree of airflow limitation and SGRQ total score.

Muscle arteriolar and venular reactivity in two models of hypertensive rats.

This study was designed to test if skeletal muscle fiber composition could influence vascular response in hypertensive rats. Muscle vessels were observed by intravital microscopy in anesthetized rats and changes in diameter were measured after local administration of endothelium-dependent and -independent vasodilators. Vascular reactivity was compared in two models of hypertension deoxicorticosterone acetate and salt load (DOCA-s) hypertensive rats and spontaneously hypertensive rats (SHR). The muscles used were: the fast-twitch glycolytic muscle, extensor digitorum longus (EDL), and the slow-twitch oxidative, soleus muscle. Maximal dilation induced by vasoactive drugs was of similar magnitude in EDL and soleus arterioles. Terminal arteriole reactivity to acetylcholine and adenosine was blunted in EDL (35% and 49% reduction, respectively) and soleus muscles (42% and 34% reduction, respectively) of SHR compared with Wistar Kyoto rats. Reactivity of DOCA-s rats to acetylcholine, adenosine, and sodium nitroprusside was reduced by 38%, 50%, 39% in EDL third- and fourth-order arterioles and by 30%, 38%, 38% in soleus fourth-order arterioles, respectively. These studies show that hypertension probably induced similar vascular changes in both muscles studied. Vascular reactivity is blunted for some vasodilator drugs and is more affected in DOCA-s rats. In addition, a preferential action for bradykinin was observed on upstream arterioles but not on venules. This effect was not observed for adenosine.

Exercise performance and skeletal muscles in patients with advanced Chagas disease.

STUDY OBJECTIVE: This study was designed to evaluate the peripheral muscle metabolic and structural characteristics in patients with advanced Chagas disease (ChD), and whether they were related with exercise performance. DESIGN: Cross-sectional study. SETTING: Outpatient cardiomyopathy clinic of a university hospital. PATIENTS AND METHODS: We studied 11 stage II patients, 8 stage III patients, and 11 healthy volunteers. All patients underwent exercise testing and peripheral muscle biopsies. The muscles were also studied in control subjects. Muscle biopsy specimens were analyzed for histochemical characteristics. In six patients, the muscle was studied ultrastructurally. RESULTS: The data demonstrate more glycolytic and less oxidative capacity of the peripheral muscle in patients with advanced ChD (increased proportion of type IIb fibers, increased proportion of fibers with low nicotinamide adenine dinucleotide diaphorase activity, high proportion of darkly stained fibers for alpha-glycerophosphate dehydrogenase activity, and lower levels of citrate synthase). Many capillaries in patients with ChD had an abnormal aspect: they were either closed or showed a thicker wall. The ultrastructural study also showed fiber atrophy and abnormal capillaries even in patients with normal functional capacity. Some muscle characteristics (enzyme activity, mean cross-sectional area of the fiber, and capillarity) related with exercise parameters (anaerobic threshold, and peak oxygen pulse). CONCLUSIONS: These findings indicate that patients with advanced ChD have decreased oxidative capacity and a shift to anaerobic metabolism in the skeletal muscle. They also suggest that muscular abnormalities are related to oxygen delivery, which is probably reduced in part by the abnormal muscle microvasculature. Those changes could affect oxygen extraction, and therefore exercise tolerance in these patients.

Estudio comparativo de características metabólicas del M. gluteus medius en equinos y bovinos / A comprative study of metabolic characteristics of M. gluteus medius in equines and bovines

Se hicieron comparaciones de las características metabólicas del M. gluteus medius de doce (12) caballos pura sangre y de cuarenta (40) vacas mestizas. La actividad de las enzimas citrato sintetasa (cs), ß-hidroxiacilCoA deshidrogenasa (HAD) y hexoquinasa (HK) fue determinada mediante técnicas fluorométricas; la actividad de la enzima lipasa lipoproteica (ALPL), los niveles de ácidos grasos libres (AGL) y triglicéridos (TG), fueron medidos por técnicas espectrofotométricas, y la masa de la LPL (mLPL) mediante el inmunoensayo ELISA. La actividad de las enzimas CS, HAD y LPL fue mayor en los equinos que en los bovinos, mientras que la mLPL fue mayor en los bovinos. Los niveles AGL y TG fueron similares en ambos grupos de animales. Se encontró una correlación positiva entre la actividad de las enzimas CS vs HAD y CS vs HK, tanto en los equinos como en los bovinos y entre la HAD vs HK en los bovinos. Asi mismo lo fue la actividad de la HAD vs la ALPL en las vacas. La ALPL también se correlacionó con la concentración de AGL en caballos y vacas, y con la concentración de TG en los caballos. Existe además correlación entre la actividad de la HAD y la concentración de TG, en los caballos. En síntesis, los resultados encontrados nos sugieren que existe una coordinación funcional entre las diversas rutas metabólicas, y que los animales más activos como los equinos, tienen un potencial aeróbico mayor que el de los animales menos activos, como los bovinos

Estudio comparativo de la proporción de tipos de fibras y de la capilaridad del M gluteus medius en equinos y bovinos / Comparative study of fibre type proportion and capillarity on gluteus medius muscle in equines and bovines

Se conoce ampliamente que la actividad o la inactividad producen adaptaciones en el músculo esquelético de humanos y animales, tendientes al mantenimiento de un metabolismo acorde con el desempeño físico. En la presente investigación, se hicieron comparaciones de los tipos de fibras y la capilaridad del M. gluteus medius entre dos especies de masa corporal similar y diferente actividad física: caballos pura sangre (n=12) y vacas mestizas (n=40). La clasificación de las fibras fue hecha a partir de colaboraciones con la reacción de la adenosina trifosfatasa (ATPasa) miofibrilar en secciones transversales de músculos preincubadas a pH ácido (4,37; 4,6 y 4,8) y pH alcalino (10,3), y la cuantificación de los capilares con la reacción alfa-amilasa-PAS. Se encontró en el M. gluteus medius tres tipos de fibras, siendo la proporción de fibras tipo I mayor en el grupo de bovinos, la de las IIA mayor en el grupo de equinos y la proporción de fibras tipo IIB, similar en ambos grupos animales. La densidad capilar, el índice capilar y los capilares adyacentes a las fibras tipo I, IIA y IIB, fueron significativamente mayores en los músculos de los equinos que en los bovinos. En conclusión, se puede afirmar que los animales más activos, con masa corporal similar, presentan carcterísticas morfológicas musculares que se traducen en un incremento del potencial oxidativo, lo cual en el caso del músculo locomotor gluteus medius, se manifiesta en una mayor capilaridad y el predominio de las fibras rápidas oxidativas-glicolíticas IIA

Muscle damage and autoantibody fixation in an experimental model of autoimmune myopathy.

An experimental model of autoimmune myopathy was designed using parental antigens (muscle mitochondrial fraction) in F1 hybrid rats (male Wistar x female Sprague-Dawley). The immune response was modulated by spleen fragment transplant from either Wistar (W) or F1. Antibody fixation and inflammatory reaction were studied in Extensor digitorum longus and soleus muscles. Immunization without spleen transplant resulted in antibody fixation mainly in capillaries and incompletely around muscle fibers; whorled fibers were found in 1/3 of F1 rats immunized with antigen from W rats. Spleen transplants from Sprague Dawley (SD) rats were usually accepted by F1; in some animals, antibodies surrounded completely muscle fibers and the percentage of animals showing soleus muscle lesions was increased. Spleen transplants from non immunized F1 were usually rejected by immunized F1; antibody reaction was found inside fibers of most of the rats, muscle damage was present in 40% of the animals immunized with W, but absent in those immunized with SD antigen. In conclusion, this model can be used to study immunological responses to alloantigens (parental to F1). Spleen fragment transplant modulates the immune response. There was discrepancy between antibody fixation and muscle damage. The immunological response was different according to muscle fiber type composition and/or microcirculatory characteristics.

Muscle damage and autoantibody fixation in an experimental model of autoimmune myopathy

An experimental model of autoimmune myopathy was designed using parental antigens (muscle mitochondrial fraction) inF1 hybrid rats (male Wistar female Sprague-Dawley). The immune response was modulated by spleen fragment transplant from either Wistar (W) or F1. Antibody fixation and inflammatory reaction were studied in Extensor digitorum longus and soleus muscles. Immunizationwithout spleen transplant resulted in antibody fixation mainly in capillaries and incompletely around muscle fibers; whorled fibers were found in 1/3 of F1 rats immunized with antigen from W rats. Spleen transplants from Sprague Dawley (SD) rats were usually accepted by F1;in some animals, antibodies surrounded completely muscle fibers and the percentage of animals showing soleus muscle lesions was increased. Spleen transplants from non immunized F1 were usually rejected by immunized F1; antibody reaction was found inside fibers of most of the rats, muscle damage was present in 40% of the animals immunized with W, but absent in those immunized with SD antigen. In conclusion, this model can be used to study immunological responses to alloantigens (parental to F1). Spleen fragment transplant modulates the immune response. There was discrepancy between antibody fixation and muscle damage. The immunological response was different according to muscle fiber type composition and/or microcirculatory characteristics.

Effect of vasoactive drugs on muscle fibre types and capillares

The effect of nitroglycerin, nifedipine, diltiazem or propranolol on fibre types and capillaries was studied in extensor digitorum longus (EDL) and soleus (S) muscles of the rat. In EDL muscle nifedipine increased the proportion of type I fibres (7.9 percent +/- 1.7 vs. 4.7 percent +/- 2.7). Nitroglycerin and dialtiazem decreased IIB fibres (40.7 percent +/- 10.6 and 37.3 percent +/- 14.6 respectively vs. 52.3 percent +/- 9.4). Propranolol increased IIB fibres to 66.3 percent +/- 8.1, while reducing IIA fibres (25.3 percent +/- 6.6 vs. 42.2 percent +/- 6.9). No changes in fibre type proportion were found in S muscle. Capillary density was increased in EDL by nitroglycerin (965 +/- 171 vs. 818 +/- 98 cap/mm2). Propranolol had a dual effect on this parameter, decreasing it in EDL to 570 +/- 85 and augmenting it in S (754 +/- 117 vs. 601 +/- 121). No change was found in capillary to fibre ratio with any of the drugs either in EDL or S muscles. In EDL all the drugs except propranolol, which had the opposite effect, decreased the area of IIA fibre per capillary around 20 percent this effect can be interpreted as a reduction of diffusion distance from blood to fibre